title: Permissive role of hypertension in the development of proteinuria and progression of renal disease in insulin-dependent diabetic patients.
abstract: BACKGROUND
  In insulin-dependent diabetic subjects, heritable factors related to hypertension and cardiovascular disease are associated with nephropathy.
  
  
  OBJECTIVE
  To determine the relationship of blood pressure, glycaemic control, family history of cardiovascular disease and sodium-lithium countertransport activity to the onset of proteinuria and decline in glomerular filtration.
  
  
  METHODS
  A retrospective analysis of the rate of onset of proteinuria and a longitudinal study of the progression of established renal disease.
  
  
  METHODS
  Guy's Hospital Diabetes Renal Clinic, a secondary referral centre.
  
  
  METHODS
  Fifty-four insulin-dependent diabetic patients with nephropathy, persistent total protein excretion rate > 500 mg/24 h, enrolled between 1978 and 1992.
  
  
  METHODS
  Rate of decline in glomerular filtration rate. Duration of diabetes at onset of nephropathy (time to proteinuria). Blood pressure and glycosylated haemoglobin at the time of diagnosis of nephropathy (baseline). Family history of cardiovascular disease and hypertension. Erythrocyte sodium-lithium countertransport activity in a subset of patients (n = 41) not being administered renal replacement therapy in 1992.
  
  
  RESULTS
  The estimated (95% confidence interval) time to proteinuria was shortened in relation to increments in diastolic blood pressure at baseline and to a family history of cardiovascular disease in both parents [1.9 (0.2-3.2) years/10 mmHg, P < 0.05 and 6.7 (-0.3-13.7) years, P < 0.07, respectively]. During follow-up 15% (n = 8) of the patients who did not require antihypertensive therapy had slower rates of decline in glomerular filtration and lower rates of sodium-lithium countertransport activity than did those who had been administered treatment [median (range): 2.88 (0.2 to -11.28) versus 7.8 (0.1 to -20.4) ml/min per 1.73 m2/year, P < 0.05 and 0.28 (0.14-0.54) versus 0.43 (0.18-0.88) mmol/l per erythrocyte/h, P < 0.03, respectively]. In this group there was an inverse relationship between the time to proteinuria and glycosylated haemoglobin (r = -0.79, P = 0.018). For the whole group a multivariate analysis showed hypertension and initial glomerular filtration rate to be related independently to the rate of decline in renal function; glycaemic control just failed to attain statistical significance (P < 0.06).
  
  
  CONCLUSIONS
  Elevation of blood pressure accelerates the onset of nephropathy and its progression; its absence, a reduced familial predisposition to cardiovascular disease, low sodium-lithium countertransport activity and good blood glucose control favour a more benign prognosis.
authors.affiliation: Unit for Metabolic Medicine, United Medical and Dental School, Guy's Campus, London, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Earle
authors.forename: A
authors.initials: A
authors.lastname: Morocutti
authors.forename: G
authors.initials: G
authors.lastname: Viberti
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology*; D012189:Retrospective Studies